Selective efflux inhibitors and related pharmaceutical compositions and methods of treatment

摘要

The present invention provides pyrazolo[1,5-a]pyrimidine compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1. Compounds and compositions according to the present invention may be used to treat cancer, including drug resistant (DR) and multiple drug resistant (MDR) cancers.

主权项

1. A pharmaceutical composition comprising an effective amount of a compound according to the chemical structure: Where R1 is an optionally substituted aryl group; R2 is an optionally substituted alkyl, aryl or heteroaryl group; R3 is H or an optionally substituted C1-C6 alkyl group; and R4 is an optionally substituted heteroarylalkyl or heteroaryl group wherein said heteroarylalkyl group is attached to the amine group of the piperazine moiety through a CH2 group and said heteroaryl group is attached to the amine group of the piperazine moiety through an acyl group; or an enantiomer, diastereomer, tautomer, or pharmaceutically-acceptable salt, in combination with one or more pharmaceutically-acceptable excipients, optionally in combination with at least one additional anticancer agent.